Infertility is a global health problem, and in the US ~1.7 million women are treated for infertility every year1. There is a strong need to promote patient friendly methods for progesterone supplementation in assisted reproductive technology (ART). Intravaginal rings are well tolerated by women, are efficacious for contraception and hormone replacement therapy, have high patient compliance 2-5, and are now in development for ART6-8. However, developing effective IVRs to deliver progesterone beyond 7 days is challenging due to limitations of current engineering processes9-10, and difficulty in controlling release rates, thus mandating drug-specific customized IVR designs. Our goal is to address these limitations by revolutionizing the engineering and manufacturing processes for intravaginal rings, using a state-of-the-art 3D printing process known as continuous liquid interface production (CLIP?)11. Using the automated CLIP process, we can engineer and manufacture IVRs with surface geometries not achievable with traditional injection molding or extrusion, which help control drug release. CLIP enables us to precisely fine-tune diffusion and release of drugs, to achieve near complete release, and also control IVR mechanical properties. Importantly, using CLIP we can manufacture IVRs that provide sustained release of progesterone to cover the entire ART treatment period in a rapid and cost effective single-step process. In this Phase I STTR project, building upon our existing data, we propose to use a state-of-the-art engineering process ? CLIP ? to develop a highly effective IVR, AnelleO-PRO, to deliver progesterone for 60 days or longer. We will implement comprehensive rational IVR design, using the highly relevant preclinical sheep model to characterize the safety and pharmacokinetic profiles of AnelleO-PRO. This multidisciplinary cutting edge approach will develop a unique and highly innovative 3D printed CLIP IVR, delivering progesterone in long- acting single administration treatment of infertility.